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Showing papers by "Raj G. Kumar published in 2016"


Journal ArticleDOI
TL;DR: PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings.
Abstract: Studies have characterized absolute levels of multiple inflammatory markers as significant risk factors for poor outcomes after traumatic brain injury (TBI). However, inflammatory marker concentrations are highly inter-related, and production of one may result in the production or regulation of another. Therefore, a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway. We used principal component analysis (PCA) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal (CSF) inflammatory profiles after TBI. Using PCA results, we defined groups (or clusters) of individuals (n=111) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0-3 and 4-5 post-injury. We identified four significant principal components (PC1-PC4) for CSF inflammation from days 0-3, and PC1 accounted for the greatest (31%) percentage of variance. PC1 was characterized by relatively higher CSF sICAM-1, sFAS, IL-10, IL-6, sVCAM-1, IL-5, and IL-8 levels. Cluster analysis then defined two distinct clusters, such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol, progesterone, estradiol, testosterone, brain derived neurotrophic factor (BDNF), and S100b; this group also had higher serum cortisol and lower serum BDNF. Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 vs. 4/5 at 6 months compared to cluster 2, after controlling for covariates. Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates. Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models. PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings. PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions.

41 citations


Journal ArticleDOI
TL;DR: Consistent with functional hypothalamic amenorrhea (FHA), menstruation resumption among pre-menopausal women occurred when serum cortisol normalized to luteal phase control levels, and for post- menopausal women, serum cortisol reductions corresponded with resolution of suppressed LH levels.
Abstract: Primary objectives: To describe hormone profiles for pre-/post-menopausal women, to monitor time to resumption of menstruation among pre-menopausal women and to describe cortisol associated LH suppression and phasic variation in other sex hormones over timeMethods and procedures: This study determined amenorrhea duration and characterized acute (days 0–7) and chronic (months 1–6) gonadotropins [luteinizing hormone and follicle stimulating hormone (LH, FSH)], sex hormones (progesterone, estradiol) and stress hormone (cortisol) profiles. Women were pre-menopausal (n = 3) or post-menopausal (n = 3). Among pre-menopausal women, menstrual cycle resolution and phase association (luteal/follicular) was monitored using self-report monthly reproductive history questionnaires. This study compared post-TBI hormone profiles, stratified by menopausal status, to hormone levels from seven controls and described 6- and 12-month outcomes for these women.Main outcomes and results: Consistent with functional hypotha...

35 citations


Journal ArticleDOI
TL;DR: PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks postinjury, according to two-step testosterone screening.
Abstract: OBJECTIVE To (1) examine relationships between persistent hypogonadotropic hypogonadism (PHH) and long-term outcomes after severe traumatic brain injury (TBI); and (2) determine whether subacute testosterone levels can predict PHH. SETTING Level 1 trauma center at a university hospital. PARTICIPANTS Consecutive sample of men with severe TBI between 2004 and 2009. DESIGN Prospective cohort study. MAIN MEASURES Post-TBI blood samples were collected during week 1, every 2 weeks until 26 weeks, and at 52 weeks. Serum hormone levels were measured, and individuals were designated as having PHH if 50% or more of samples met criteria for hypogonadotropic hypogonadism. At 6 and 12 months postinjury, we assessed global outcome, disability, functional cognition, depression, and quality of life. RESULTS We recruited 78 men; median (interquartile range) age was 28.5 (22-42) years. Thirty-four patients (44%) had PHH during the first year postinjury. Multivariable regression, controlling for age, demonstrated PHH status predicted worse global outcome scores, more disability, and reduced functional cognition at 6 and 12 months post-TBI. Two-step testosterone screening for PHH at 12 to 16 weeks postinjury yielded a sensitivity of 79% and specificity of 100%. CONCLUSION PHH status in men predicts poor outcome after severe TBI, and PHH can accurately be predicted at 12 to 16 weeks.

27 citations



Journal ArticleDOI
TL;DR: In this article, the structural and photo physical properties of fluorescent nanodiamonds containing nitrogen-vacancy (NV) centers were discussed using two different purification methods; chemical etching (H2SO4:HNO3) and air oxidation (450 °C).
Abstract: Fluorescent nanodiamonds (FNDs) with high photo stability at a subwavelength scale are highly desirable for nano-photonics and bio-imaging applications. Nanodiamonds (NDs) with embedded fluorescent color centers made by ion-implantation need to be purified to remove the sp2 layer on their surfaces which significantly degrades the optical properties. In this work, we discuss the structural and photo physical properties of NDs containing nitrogen-vacancy (NV) centers prepared by two different purification methods; chemical etching (H2SO4:HNO3) and air oxidation (450 °C). Chemically etched NDs show better uniformity in their shape, de-aggregation and higher dispersibility in water as compared to air oxidized ones. On the other hand it is observed that air oxidation is more effective in removing the sp2 layer and allows a higher fluorescence photon flux. Therefore, we suggest that air oxidation is more appropriate for bright fluorescent sources, and chemical etching is more appropriate for fluorescent markers in bio-imaging applications with high uniformity in shape and good dispersibility.

9 citations